1. Technical Field of the Invention
The present invention relates to cosmetic/dermatological compositions comprising at least one inhibitor of at least one excitatory amino acid, such as at least one aspartate or glutamate, for the treatment of sensitive human skin, for example the scalp, the-area around the eyes and the mucous membranes.
2. Description of the Prior Art
It is known to this art that certain skin types are more sensitive than others. The symptoms of xe2x80x9csensitive skinxe2x80x9d were hitherto poorly characterized and the problem of these skin types was consequently poorly defined; what process was involved in skin sensitivity was unknown. Certain researchers believed that sensitive skin was skin which reacted to cosmetic products, while others considered it was skin which reacted to a variety of external factors, not necessarily associated with cosmetic products.
Certain tests have now been developed in an attempt to characterize sensitive skin, for example tests utilizing lactic acid and DMSO which are known irritants. See, for example, the article by K. Lammintausta et al., Dermatoses, 36, pages 45-49 (1988); and the article by T. Agner and J. Serup, Clinical and Experimental Dermatology, 14, pages 214-217 (1989). However, these tests for characterizing sensitive skin were less than completely successful.
Moreover, sensitive skin was likened to allergic skin.
Since the characteristics of sensitive skin were not well known, it was hitherto very difficult to treat such skin types, and these were treated indirectly, for example by limiting application to the skin of products of irritant nature, such as surfactants, preservatives or fragrances as well as certain active agents, these typically being formulated into a variety of cosmetic compositions.
Many clinical tests have been carried out by the assignee hereof to determine the symptoms associated with sensitive skin. These symptoms are, in particular, subjective signs, which are essentially dysaesthetic sensations. By the term xe2x80x9cdysaesthetic sensationsxe2x80x9d is intended the more or less painful sensations experienced in a particular region of skin, such as stinging, tingling, itching or pruritus, burning, heating, discomfort, tautness, etc.
The assignee hereof has also been able to demonstrate that sensitive skin is not allergic skin. The essential characteristic of sensitive skin is believed to be a mechanism of response to external factors, which can affect any individual, although individuals with so-called xe2x80x9csensitivexe2x80x9d skin react faster thereto than others. This mechanism is not immunological.
Thus, the assignee hereof has now found that sensitive skin can be divided into two major clinical forms: irritable and/or reactive skin and intolerant skin.
Irritable and/or reactive skin is a skin which reacts by pruritus, i.e. by itching or stinging, to various factors or challenges such as the environment, emotions, foods, the wind, rubbing, shaving, soap, surfactants, hard water having a high calcium concentration, temperature variations, wool, etc. In general, these signs are associated with dry skin or with skin afflicted with erythema.
Intolerant skin is a skin which reacts, by sensations of heating, tautness, tingling and/or redness, to various factors and challenges such as the environment, emotions, foods, etc. In general, these signs are associated with hyperseborrhoeic or acneic skin, and with erythema.
xe2x80x9cSensitivexe2x80x9d scalps have a more univocal clinical semeiology: the sensations of pruritus and/or of stinging and/or heating are essentially triggered by local factors such as rubbing, soap, surfactants, hard water having a high calcium concentration, shampoos or lotions, permanent-wave products, and the like. These sensations are also sometimes triggered by factors such as the environment, emotions and/or foods. Erythema and hyperseborrhoea of the scalp and the presence of dandruff are often associated with the above signs.
Moreover, in certain anatomical regions such as the major folds (groin, genital, axillary, popliteal, anal and submammary regions and in the crook of the elbow) and the feet, sensitive skin is reflected in pruriginous sensations and/or dysaesthetic sensations (heating, stinging) associated in particular with sweat, rubbing, wool, surfactants, hard water having a high calcium concentration and/or temperature variations.
In order to determine whether skin is sensitive or not, a test has also been developed by the assignee hereof. After having carried out a large number of tests for the purpose of defining sensitive skin, it has surprisingly been found that there is a relationship between individuals with sensitive skin and those who react to topical application of capsaicin.
The capsaicin test entails applying 0.05 ml of a cream containing 0.0750% capsaicin to about 4 cm2 of skin and in noting the appearance of subjective signs caused by this application, such as stinging, burning and itching. In individuals with sensitive skin, these signs appear between 3 and 20 minutes after topical application and are followed by the appearance of an erythema which begins at the periphery of the zone of application.
Capsaicin causes, in particular, a release of neuropeptides, and in particular tachykinins which originate from sensitive nerve endings in the epidermis and the dermis. It has been observed that the physiopathological schema common to all the sensitive skin conditions is associated with a large capacity to release tachykinins and more particularly substance P into the skin. The dysaesthetic manifestations which are caused by the release of neuropeptides are referred to as xe2x80x9cneurogenicxe2x80x9d.
Substance P is a polypeptide which is produced and released by sensitive nerve endings. It induces, in particular, a degranulation of mastocytes, effecting the release of serotonin and a cascade of biochemical events resulting in an inflammatory reaction. The release of substance P by sensitive nerve endings can be controlled by various active agents including excitatory amino acids such as glutamate and/or aspartate.
It has now unexpectedly been determined that nerve fibers present in the epidermis and/or the dermis contain excitatory amino acids such as aspartate and/or glutamate, and, thus, that the release of aspartate and/or glutamate close to sensitive nerve endings activates the release of substance P and, hence, the cascade of biochemical events which results in the more or less pronounced nociceptive reactions.
Accordingly, administration of an inhibitor of at least one excitatory amino acid elicits a preventive and/or curative effect on sensitive skin since, by decreasing the release and/or synthesis of excitatory amino acids by nerve fibers and/or by decreasing their binding, the activity attributed to these excitatory amino acids is reduced.